Asymmetric Synthesis of Diverse P(V) Compounds Bearing a C–P Bond via Desymmetrization of Phosphonic Dichlorides Catalyzed by a Chiral Bicyclic Imidazole

High Resolution Image Download MS PowerPoint Slide Chiral phosphorus(V) compounds bearing one or two C–P bonds exhibit significant utility in pharmacy and catalysis. Although several established methods enable stereoselective access to these P-stereogenic compounds, achieving direct enantiocontrol at phosphorus via catalytic P(V)–heteroatom bond formation remains challenging. Herein, we present a highly efficient strategy to synthesize such chiral P(V) compounds through the asymmetric desymmetrization of phosphonic dichlorides catalyzed by a readily accessible bifunctional chiral bicyclic imidazole. The synergistic combination of Lewis base catalysis and hydrogen bond catalysis is responsible for the high reactivity and stereoselectivity. The one-pot sequential process combining the catalytic desymmetrization and the enantiospecific S N 2 displacement delivers a large number of chiral P(V) compounds with excellent yields and enantioselectivities. This protocol establishes a versatile platform for the concise synthesis of structurally diverse P-chirogenic motifs relevant to high-value bioactive molecules.